Correlation of singlet-triplet gaps for aryl carbenes calculated by MINDO/3, MNDO,AM1, and PM3 with Hammett-type substituent constants

Heats of formation, atomic charges, and geometries of some 110 structures involving substituted singlet and triplet phenyl and 4,4-dimethyl-1,4-dihydronaphthalene carbenes and the corresponding diazomethanes were calculated by MINDO/3, MNDO, AM1, and PM3 semiempirical molecular orbital methods. The singlet-triplet gaps for AM1 and PM3 calculations for the para derivatives in both systems have been successfully correlated with Brown σ⁺ constants. Good correlations with σ⁺ were found for the charges on the carbenic centers of the singlets as well as with the energy barrier for rotation of the aryl group about the C-C single bond in substituted singlet phenylcarbenes. Comparisons of these results with experimental data indicate that AM1 and PM3 are much better than MNDO and MINDO/3 in predicting the intrinsic substituent effects in singlet carbenes.     

Correlation analysis of substituent effects on the acidity of benzoic acids by the AM1 method

Theoretical analysis of the electronic effect of aromatic substituents was done with the use of the AM1 computational procedure. The gas-phase acidity of substituted benzoic acids was linear with the difference in the heat of formation between corresponding benzoic acids and benzoate anions, the energy of the highest occupied molecular orbital, and the net charge on the acidic oxygen atoms of the corresponding benzoate anions. The Hammett σ constant was linearly correlated with the net charge on the atoms of the acid moiety of substituted benzoic acids. The AM1 computational procedure satisfactorily reproduced the electronic properties of a wide variety of substituents.     

Substituent effects on the acidity of weak acids. 3. Phenols and benzyl alcohols

The gas-phase acidities of meta- and para-substituted phenols have been calculated at the B3LYP/6-311+G, MP2/6-311+G, MP2/6-311++G, and MP2/6-311+G(2df,2pd) theoretical levels. The larger basis sets give the more satisfactory DeltaHacid values that are correlated with the observed acidities with a slope close to unity. They are systematically about 2 kcal/mol too small. The acidities of most substituted phenols are linearly related to those of the corresponding substituted benzoic acids and benzyl alcohols. Here, the substituent effect is a Coulombic interaction (field effect) of the distributed charge in the benzene ring with the negative charge of the anionic center. The exceptions are strong para-substituted pi-acceptors such as NO(2) and CHO, and to a smaller extent, CN and CF(3). Here there is direct charge transfer from the phenoxide oxygen to the substituent.     

Hydrocarbon acidities calculated with MINDO/3, MNDO,and AM1

Acidities of 32 hydrocarbons have been calculated using MINDO/3, MNDO, and AM1. All three semiempirical procedures have systematic errors and reproduce experimental acidities poorly. A linear correlation, however, does exist between the calculated and experimental results. Correction of the AM1 or MNDO acidities leads to good agreement with literature values even for acids, such as methane and ethylene, whose conjugate bases are small localized anions. Predictions for several hydrocarbons are given.     

Analysis of a large data base of electrostatic potential derived atomic charges

A large data base of 6-31G*, MNDO, AM1, and PM3 electrostatic potential (ESP) derived point charges of amino acids and monosaccharides is analyzed. We find that MNDO correlates well with 6-31G* ESP derived point charges, while AM1 and PM3 do so quite poorly. Furthermore, scaling MNDO ESP derived point charges enhances the ability of MNDO to reproduce 6-31G* results. We used our data base to attempt to derive a 6-31G* transferable charge model at an atom-by-atom level. We find that it is simple to derive a transferable model for monosaccharides, but for the amino acids statistical difficulties make this a less attractive approach. The transferable charge model for the monosaccharides is slightly better than MNDO, but scaled MNDO charges perform significantly better than the transferable model. We also carried out a QMD simulation on the alanine dipeptide to assess the fluctuations that would be expected in atomic point charges during the course of an MD simulation. Relatively large charge fluctuations are observed and their impact on molecular simulation is addressed. © 1992 by John Wiley & Sons, Inc.     

Substituent effects on the acidity of weak acids. 2. Calculated gas-phase acidities of substituted benzoic acids

To investigate the origin of substituent effects on the acidity of benzoic acids, the structures of a series of substituted benzoic acids and benzoates have been calculated at the B3LYP/6-311+G* and MP2/6-311+G* theoretical levels. The vibrational frequencies were calculated using B3LYP/6-311+G* and allowed corrections for the change in zero-point energies on ionization, and the change in energy on going from 0 K (corresponding to the calculations) to 298 K. A more satisfactory agreement with the experimental values was obtained by energy calculations at the MP2/ 6-311++G* level using the above structures. The resulting Delta H(acid) values agree very well with the experimental gas-phase acidities. The energies of compounds with pi-electron-accepting or -releasing substituents, rotated to give the transition state geometries, provided rotational barriers that could be compared with those found for the corresponding substituted benzenes. Isodesmic reactions allowed the separate examination of the substituent effects on the energies of the acids and on the anions. Electron-withdrawing groups stabilize the benzoate anions more than they destabilize the benzoic acids. Electron-donating groups stabilize the acids and destabilize the anions by approximately equal amounts. The gas-phase acidities of meta- and para-substituted benzoic acids are linearly related. This is also found for the acidities of substituted phenylacetic acids and benzoic acids. Since direct pi-electron interactions are not possible with the phenylacetic acids, this indicates that the acidities are mainly controlled by a field effect interaction between the charge distribution in the substituted benzene ring and the negative charge of the carboxylate group. The Hammett sigma(M) and sigma(P) values are also linearly related for many small substituents from NO(2) through the halogens and to OH and NH(2). Most of the other substituents fall on a line with a different slope     

Theoretical calculations of the structure of a donor—acceptor stilbene, azobenzene and related molecules

The structures of a substituted stilbene, azobenzene, and two isomeric benzylidene anilines containing the 4-dimethyl-amino group at one end of the molecule and the 4′-nitro group at the other, have been calculated using the semiempirical MNDO, AM1, and PM3 methods and the ab initio HF/3-21G method. The results are compared with experimental data where available. The MNDO method gives a very poor account of the geometry of the stilbene, but both the AM1 and PM3 methods correctly predict the planarity of the substituted stilbene and nitrobenzylidene aniline but erroneously predict a non-planar structure for the azobenzene. In contrast, the ab initio method predicts planar structures for the substituted stilbene, azobenzene, and nitrobenzylidene aniline, and a twisted structure for the isomeric benzylidene nitroaniline, in line with crystallographic data. This loss of planarity for the benzylidene nitroaniline is almost certainly responsible for its smaller non-linear activity and for the hypsochromic shift observed in its low energy absorption band relative to the other molecules.     

1,2,3-triazol-1-imines. 2. Electric dipole moments and semiempirical studies of some 2-aryl-N-benzoyl-4,5-dimethyl-1,2,3-triazol-1-imines

Electric dipole moments of some 2-aryl-N-benzoyl-4,5-dimethyl-1,2,3-triazol-1-imines were measured in carbon tetrachloride solution and the results compared with those derived computationally using MNDO, AM1 and PM3. Good correlation of the dipole moments with σ⁺ substituent constants was obtained.     

MNDO,AM1 and PM3 calculations in the study of the energy and structure of quinazolone tautomers

MNDO, AM1, and PM3 calculations were used to study the tautomeric forms of quinazolones. The relative energy of the tautomers closest to the experimental value was obtained using the AM1 and PM3 methods. The keto-enol tautomeric equilibrium of quinazolones in the gas phase is shifted toward the ketone form.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1246–1251, September, 1993.     

Substituent effects in π-(tricarbonylchromium)arenes: V. Thermodynamic dissociation constants of some substituted π-(tricarbonylchromium)benzoic acids

The thermodynamic dissociation constants of a series of 38 substituted π-(tricarbonylchromium)benzoic acids in 50% aqueous ethanol at 25°C have been determined. The results require revision of some literature values.The pK_a^*-values of the π-(tricarbonylchromium)benzoic acids were correlated with the electronic substituent parameters in terms of the Yukawa-Tsuno equation. The reaction constant (ρ) decreases from 1.4 for the benzoic acids to 0.8 for the π-(tricarbonylchromium)benzoic acids, reflecting the decreased ability of the complexed aromatic system to transmit electronic substituent effects. For the alkylsubstituted π-(tricarbonylchromium)benzoic acids, conformational effects of the Cr(CO)₃ group can account for some of the anomalies observed. The substituent parameters, σ_meta and σ_para, of the π-(Cr(CO)₃)phenyl group as a substituent were derived from the dissociation constants of the complexed phenylbenzoic acids.     

Atomic charges derived from semiempirical methods

It is demonstrated that semiempirical methods give electrostatic potential (ESP) derived atomic point charges that are in reasonable agreement with ab initio ESP charges. Furthermore, we find that MNDO ESP charges are superior to AM1 ESP charges in correlating with ESP charges derived from the 6-31G* basis set. Thus, it is possible to obtain 6-31G* quality point charges by simply scaling MNDO ESP charges. The charges are scaled in a linear (y = Mx) manner to conserve charge. In this way researchers desiring to carry out force field simulations or minimizations can obtain charges by using MNDO, which requires much less computer time than the corresponding 6-31G* calculation.     

Organic reactivity in liquid ammonia

Liquid ammonia is a useful solvent for many organic reactions including aliphatic and aromatic nucleophilic substitution and metal-ion catalysed reactions. The acidity of acids is modified in liquid ammonia giving rise to differences from conventional solvents. The ionisation constants of phenols and carbon acids are the product of those for ion-pair formation and dissociation to the free ions. There is a linear relationship between the pK(a) of phenols and carbon acids in liquid ammonia and those in water of slope 1.68 and 0.7, respectively. Aminium ions exist in their unprotonated free base form in liquid ammonia. The rates of solvolysis and aminolysis by neutral amines of substituted benzyl chlorides in liquid ammonia show little or no dependence upon ring substituents, in stark contrast with the hydrolysis rates of substituted benzyl halides in water which vary 10(7) fold. However, the rates of the reaction of phenoxide ions and amine anions with 4-substituted benzyl chlorides gives a Hammett ρ = 1.1 and 0.93, respectively. The second order rate constants for the substitution of benzyl chlorides by neutral and anionic amines show a single Br?nsted β(nuc) = 0.21 whereas those for substituted phenoxide ions generate a Br?nsted β(nuc) = 0.40. The rates of aromatic nucleophilic substitution reactions in liquid ammonia are much faster than those in protic solvents indicating that liquid ammonia behaves like a typical dipolar aprotic solvent in its solvent effects on organic reactions. Nitrofluorobenzenes (NFB) readily undergo solvolysis in liquid ammonia but oxygen nucleophiles, such as alkoxide and phenoxide ions, displace the fluorine of 4-NFB in liquid ammonia to give the corresponding substitution product with little or no competing solvolysis product. The Br?nsted β(nuc) for the reaction of 4-NFB with para-substituted phenoxides is 0.91, indicative that the decomposition of the Meisenheimer σ-intermediate is rate limiting. The aminolysis of 4-NFB occurs without general base catalysis by the amine and the second order rate constants generate a Br?nsted β(nuc) of 0.36, which is also interpreted in terms of rate limiting breakdown of the Meisenheimer σ-intermediate.     

Is the Hammett's constant free of steric effects?

In this work, we have explored the validity of the hypotheses on which rest the Hammett's approach to quantify the substituent effect on a reaction center, by applying two DFT energy decomposition schemes. This is performed by studying the change in the total electronic energy, ΔΔE, associated with a proton transfer isodesmic equilibrium. For this reaction, two sets of substituted benzoic acids and their corresponding benzoate anions have been considered. One of these sets contains para- and meta-substitutions, whereas the other one includes ortho-substituted benzoic acids. For each case, the gas phase change in the total electronic energy has been calculated, and two DFT energy decomposition schemes have been applied. The experimental σ(X) was found to be nearly proportional to the computed ΔΔE. The results for the para- and meta-substituted benzoic acids lead to the conclusion that it is possible to treat separately and, in an additive manner, the electrostatic and steric contributions; and also that the Hammett constant depends mainly on the electronic contributions to the free energy, while the steric contribution is negligible. However, the results for the ortho-substituted cases lead to the conclusion, as was assumed by Hammett, that there are significant qualitative differences between the effects on a reaction site of substituents in the meta- and para-positions and those in the ortho-position.     

Enthalpy of formation of thiophene derivatives

The enthalpy of formation in the gas phase has been calculated for 21 carbonyl compounds of the thiophene series with the aid of the PM3, MINDO, AM1, and MNDO semiempirical quantum-chemical methods. Comparison of them with experimental data showed that the best linear correlation was achieved with the PM3 method. The latter in conjunction with a developed linear regression equation has been used to predict the enthalpy of formation of 22 carboxylic acids and ketones of the thiophene series.     

Theoretical study of the proton affinities of 2-, 3-, and 4-monosubstituted pyridines in the gas phase by means of MINDO/3, MNDO,and AM1

Proton affinities (PAs) of 2-, 3-, and 4-monosubstituted pyridines in the gas phase are calculated using the MINDO/3, MNDO, and AM1 methods. The following substituents are considered: F, Cl, CN, CH₃, CF₃, CHO, NO₂, NH₂, N(CH₃)₂, OCH₃, and SCH₃. The results are compared with experimental values. It is found that all MINDO/3 PAs are ca. 6% too high (mean value) compared to the experimental results; on the other hand, the MNDO values are ca. 7% too low (mean value). However, a much better agreement has been observed for the AM1 method where the theoretical values are only ca. 2.4% too low (mean value). Correlations between the calculated proton affinities on one hand and the charges on the acid H atom and Hammett constants on the other hand are studied. Particularly good linear relationships are found for the 4-monosubstituted compounds within the AM1 formalism.     

Synthesis of Diels–Alder adducts of N-arylmaleimides by a multicomponent reaction between maleic anhydride, dienes, and anilines

Abstract  

We have carried out the synthesis and characterization of some hexahydroisoindolyl benzoic acids and their corresponding ethyl esters by a multicomponent reaction (MCR) between aminobenzoic acids or aminobenzoates, maleic anhydride, and isoprene in the absence of catalysts. According to additional experiments, the MCR takes place by sequential formation of N-arylmaleamic acids from the aminobenzoic acids or aminobenzoates and maleic anhydride, Diels–Alder adducts of the acids and isoprene, and finally the imides. The ¹H NMR data (coupling constants) of the adducts suggested that the preferred conformation of the corresponding cyclohexene rings is a syn-boat, a fact supported by a density functional theory (DFT) conformational analysis and DFT calculations of the spin–spin coupling constants of the corresponding conformers. Our MCR synthetic methodology was tested successfully in the synthesis of other adducts, for which cyclopentadiene and other anilines were employed.     

Generation and reactions of substituted phenide anions in an electrospray triple quadrupole mass spectrometer

Substituted benzoic acid anions undergo decarboxylation in the medium-pressure region of an electrospray ion source yielding in most cases the correspondingly substituted phenide anions in high yield. The location of the anionic center is specified by the position of the carboxylic group. The only exceptions are compounds with substituents containing acidic hydrogen atoms, like OH and NH(2) groups. For such compounds, either an intra- or an intermolecular (mediated by the molecules of methanol or water) proton transfer from the more acidic position to the benzene ring is observed. The generated anions can be selected using the first quadrupole for studying their ion-molecule chemistry in the second quadrupole of a triple quadrupole mass spectrometer. Their reactions with CO(2), O(2), CH(3)COCH(3) and CCl(4) may serve as typical examples. The general applicability of this method for the generation of phenide anions has been confirmed on three different mass spectrometers. Experiments performed using carboxylic acids other then benzoic acid and its derivatives show that this method is not limited to phenide anions and can be used for the generation of a much wider range of carbanions in the gas phase.     

Evaluation of PM3, AM1, and MNDO for calculation of higher energy ionization potentials

Higher ionization energies were calculated with PM3, AM1, and MNDO for three series of molecules, representative small molecules, molecules containing heteroatoms, and sterically congested alkenes. Values from PM3, AM1, and MNDO were compared to experimental values. In most instances, the semiempirical calculations correctly predict the ordering of higher ionization energies. In the absence of steric hindrance, MNDO is the method of choice. Within groups of molecules, AM1 performs better on hydrocarbons, especially twisted hydrocarbons, than PM3. PM3 commonly gives sigma orbitals which are too high in energy compared to related pi orbitals. PM3 performed better than AM1 with molecules containing oxygen, but failed to give the correct geometry for hydrogen peroxide.     

Reactions of Azolium cations. II [1]. Regioselective N2 alkylation of 5-aryltetrazoles with isopropyl alcohol in sulfuric acid media: Effect of electronic properties of aryl substituents on the reaction rate

Kinetics of regioselective N2 alkylation of a series of 5-(R-phenyl)tetrazoles with isopropyl alcohol has been studied in 88.2, 94.3, and 98.3% (w/w) sulfuric acid at 25°. The true rate constants were evaluated, logarithms of which were found to correlate with σ° constants of phenyl substituents as log k = ?0.488 σ° ? 0.417. Small value of Hammett constant ρ is evidence of a considerable isolation of the reaction center from the influence of the substituent at position C5 of the heteroring. This conclusion is confirmed by results of MNDO quantum chemical calculations of a series of 5-substituted tetrazolium cations. A correlation between logarithms of the true rate constants and the calculated net effective charges on atoms N2(N3) for 5-(R-phenyl)tetrazolium cations has been revealed. © 1995 John Wiley & Sons, Inc.     

Substituent interaction effects in aromatic molecules in RP-HPLC with acetonitrile-water and tetrahydrofuran-water eluents

Summary Retention volumes of monosubstituted benzenes, benzoic acids, phenols and anilines have been measured in reversed-phase liquid chromatography. Buffered acetonitrile-water and tetrahydrofuran-water eluents were used with an octadecylsilylsilica adsorbent. From the net retention volumes a substituent interaction effect was calculated and described with the linear free energy relationship developed by Taft. The positive sign of the values of the -parameters, figuring in this relationship, was interpreted in terms of hydrogen bonding between the solutes and the eluent.